The present invention relates to a process for alkylating 2-hydroxyphenyl-benzotriazoles, which are effective in absorbing ultra violet radiation. In a further aspect, the present invention relates to novel alkylated 2-hydroxyphenyl-benzotriazoles, to novel cosmetic or dermatological sunscreen compositions containing alkylated 2-hydroxyphenyl-benzotriazoles, and to their use as UV screening agents.
Winter et al., U.S. Pat. No. 4,587,346 discloses a process for alkylating 2-(2-hydroxy-5-methylphenyl)-2H-benzotriazoles by reaction with alkene compound ions in the presence of a catalyst. The process produces random mixtures of isomers.
UV screening compositions containing 2-hydroxyphenyl-benzotriazoles are described in European Patent Publications EP 0711778 A (Herve et al., U.S. Pat. No. 5,569,451), EP 0392883 A (Gerard et al., U.S. Pat. No. 5,089,250), Ching, U.S. Pat. Nos. 4,316,033 and 4,349,602, and International Patent Application WO 94/06404 (Hansenne et al., U.S. Pat. No. 5,089,250).
It has been found that alkylated 2-(2-hydroxy-5-methylphenyl)-2H-benzotriazoles can be obtained in substantially pure form. Further, it has been found that certain novel 2-hydroxyphenyl-benzotriazoles have improved solubility and extinction coefficients, and are more economical to prepare than those of the prior art quoted above.
The present invention is a process for the preparation of compounds of the formula: 
wherein
R1 is alkyl; R2, R3, R4, R5, and R6 are, independently, hydrogen, alkyl or alkenyl; X is hydrogen, halogen, alkyl or alkoxy; and the dotted bond is an optional bond,
which includes the steps of
a) reacting a compound of the formula: 
with a compound of the formula: 
to obtain a compound of the formula: 
b) heating the compound of formula II obtained in step a) to yield a compound of the formula 
and if desired,
c) hydrogenating the double bond between R2 and R3 in the compound of formula I A to obtain a compound of formula I wherein the dotted bond is absent;
wherein in the above formulae IA, II, III and IV, R1, R2, R3, R4, R5, R6, X and the dotted line are as defined in formula I, and Y is a leaving group.
The following compounds are novel, and are also part of the present invention: compounds of formula I above, wherein X, R1, R2, R3, R4, R5, R6 and the dotted bond are as defined in claim 1, with the proviso that if the dotted bond is present, one of R2, R4, R5, and R6 is alkenyl, and if the dotted bond is absent, one of R2 and R6 is alkenyl or branched alkyl. In addition, the following compounds are also novel:
2-(Benzotriazole-2-yl)-4-methyl-6-(1-octen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-octen-2-yl)-phenol
2-(Benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-6-(1-hexen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(1-decen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(1-hexen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(1-dodecen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6- (1-hexadecen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-octyl)-phenol,
2-(Benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-6-(3-hexyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-hexyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-decyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-dodecyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-hexadecyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-2-octenyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-3-octyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-1-octen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-3-octyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-3-octen-2-yl)-phenol, and
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-2-octyl)-phenol.
Further examples of novel compounds of the present invention are:
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-2,6-octadienyl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl- 1,6-octadienyl)-phenol, and
2-(Benzotriazole-2-yl)-4-methyl-6-(3,7-dimethyl-3,6-octadienyl)-phenol.
Another aspect of the invention relates to novel cosmetic or dermatological UV light screening compositions containing a 2-hydroxyphenyl-benzotriazole of formula I above, wherein X, R1, R2, R3, R4, R5, R6, and the dotted bond are as defined in claim 1, with the proviso that either R4 or R5 is an alkyl having at least 2 carbon atoms, or is alkenyl. In yet another aspect, the invention relates to novel UV light screening compositions containing a 2-hydroxyphenyl-benzotriazole of formula I above, wherein X, R1, R2, R3, R4, R5, R6, and the dotted bond, are as defined in claim 1, with the proviso that either R4 or R5 is an alkyl having at least 2 carbon atoms or is an alkenyl; and at least one additional UV-A and/or UV-B screening agent. Finally, the present invention relates to a method for protecting hair or skin from damage caused by UV-radiation comprising administering to the hair or skin prior to exposure to a UV-radiation source a composition comprising an UV-radiation blocking amount of the novel 2-hydroxyphenyl-benzotriazoles as defined earlier, as UV light screening agents.
Especially preferred compounds of formula I for use as UV light screening agents are:
2-(Benzotriazole-2-yl)-4-methyl-6-(1-octen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-6-(1-hexen-3-yl)-phenol,
2-(Benzotriazole-2-yl)-4-methyl-6-(3-octyl)-phenol, and
2-(Benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-6-(3-hexyl)-phenol.
The most preferred compound is 2-(Benzotriazole-2-yl)-4-methyl-6-(1-octen-3-yl)-phenol.
As used herein the term xe2x80x9calkylxe2x80x9d denotes saturated straight or branched chain hydrocarbon groups containing 1 to 21, preferably 1 to 8 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, sec. butyl, isobutyl, pentyl, neopentyl, hexyl, 2-ethyl-hexyl, and octyl. Similarly, the term xe2x80x9calkoxyxe2x80x9d denotes saturated straight or branched chain hydrocarbon groups which are bound through an oxygen atom and which contain 1 to 21, preferably 1 to 8 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec. butoxy, isobutoxy, pentyloxy, neopentyloxy, hexyloxy, 2-ethyl-hexyloxy and octyloxy. The term xe2x80x9calkenylxe2x80x9d denotes straight or branched chain hydrocarbon groups containing at least one double bond and 2 to 21, preferably 2 to 8, carbon atoms. Examples of such alkenyl groups are propen-2-yl, propen-3-yl, buten-3-yl, buten-4-yl, penten-4-yl, and penten-5-yl. The term xe2x80x9chalogenxe2x80x9d denotes fluoro, chloro, bromo and iodo.
A preferred group of compounds within formula I are those wherein the dotted bond is present. Also preferred are compounds of formula I wherein R5 and R6 are hydrogen. Further preferred are compounds wherein one of R2, R3, or R4 is an alkyl having at least three carbon atoms, and the other two are hydrogen. The total number of carbon atoms in R2 to R6 is preferably 3 to 21, more particularly 3 to 9 carbon atoms, most preferably 3 to 5. Especially preferred are compounds of formula I wherein R2 and R3 are hydrogen and R4 is an alkyl having 3 to 5 carbon atoms. R1 is preferably methyl or 1,1,3,3-tetramethylbutyl. X is preferably hydrogen, methoxy or chloro, and most preferably hydrogen.